The Staphylococci make up a medically important genera of microbes known to cause several types of diseases in humans. S. aureus is a Gram positive organism which can be found on the skin of healthy human hosts. It is responsible for a large number of bacteremias, where its portal of entry can be the skin, lungs, urinary tract or infected intravascular devices (Steinberg et al., (1996)) Clin. Infect. Dis. 23: 255–259; Røder et al., (1999) Arch. Intern. Med. 159: 462–469). It can cause fatal endocarditis or damage to the heart and, due to its exotoxin, can cause death via “Toxic Shock” (Frimodt-Møller et al., (1997) Clin. Microbiol. Infect. 3: 297–305; Sanabria et al., (1990) Arch. Intern. Med. 150: 1305–1309).
Only S. aureus and Staphylococcus epidermidis, of the nineteen species of Staphylococcus described in Bergey's Manual (1992), have significant interactions with humans. They are among the normal flora of humans, and are found on nasal passages, skin and mucous membranes. S. aureus, when pathogenic in humans, can cause a number of suppurative (pus-forming) infections, as well as food poisoning, endocarditis, and toxic shock syndrome.
S. aureus causes superficial skin lesions, such as boils, styes and furunculosis; more serious infections include pneumonia, mastitis, phlebitis, meningitis, and urinary tract infections, in addition to osteomyelitis and endocarditis. S. aureus is also a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with inserted and implanted medical devices. Lastly, S. aureus causes food poisoning through the release of enterotoxins into food, and toxic shock syndrome through the release of superantigens into the blood stream. S. aureus also secretes two types of toxin with superantigen activity: 1) enterotoxins, of which there are six antigenic types (named SE-A, B, C, D, E and G) and 2) toxic shock syndrome toxin (TSST-1).
S. aureus has been successfully treated with the penicillin derivative Methicillin in the past, but is now becoming increasingly resistant (MRSA—Methicillin Resistant S. aureus) to this antibiotic (Harbath et al., (1998) Arch. Intern. Med. 158: 182–189.). For example, S. aureus endocarditis mortality can range from 26–45%, and combined β-lactam/aminoglycoside therapy is proving increasingly ineffective in disease eradication (Røder et al., (1999) Arch. Intern. Med. 159: 462–469). However, MRSA infections continue to be sensitive to treatment with vancomycin, which is the drug of last resort. Infections caused by MRSA have been increasing in children and adults; isolates have been found in 97% of all large, university-based teaching hospitals in the United States. Since 1996, three cases of vancomycin resistant S. aureus have been reported. This new strain represents a particularly dangerous development of an aggressive bacterial pathogen which does not respond to any known antibiotic. The emergence of resistance to vancomycin has the potential to result in untreatable (and thus fatal) S. aureus infections.
It is no longer uncommon to isolate S. aureus strains which are resistant to most of the standard antibiotics, and thus there is an unmet medical need and demand for new anti-microbial agents, vaccines, drug screening methods, and diagnostic tests for this organism.